The aim of the proposed research is to develop and validate a gene therapy protocol for the sustained local release of Insulin-Like Growth Factor-I (IGF-I) in amounts sufficient to promote healing of equine articular cartilage. IGF-I has an important role in cartilage development and homeostasis, and in previous studies has been shown to promote healing in experimentally injured cartilage. An important limitation, however, has been the inability to sustain therapeutic levels of IGF-I at the site of injury. To overcome this limitation, I would use an adenovirus vector to introduce an IGF-I gene construct into equine chondrocytes. The transfected cells would then be imported into experimentally injured joints, with the resulting repair tissue examined at predetermined intervals. Thereafter, I would assess donor cell survival and quantify local IGF-I gene expression, correlations being drawn with biomechanical, molecular biological, histological and biomechanical analyses that reflect various aspects of the healing process.